The purpose of the proposed Program Project Grant is to bring together sociological, psychological, and biological levels of analyses to bear on the relationships among and mechanisms underlying social isolation, feelings of loneliness, health, and the aging process. Social relationships are fundamental to emotional fulfillment, behavioral adjustment, and cognitive function. Recent research has shown that emotional closeness in relationships increases with age. Yet the number of social relationships decreases and social events triggering loneliness continue in the older adult. Moreover, they are physically aging and tend to be less resilient so these psychosocial challenges could potentially leave them vulnerable to feelings of loneliness, dysphoria, elevated and prolonged neuroendocrine stress responses, and ill health. Loneliness predicts morbidity and mortality from broad based causes in later life even after controlling for health behaviors and biological risk factors. Understanding the antecedents of feelings of loneliness and their consequences for mental and physical health can thus be studied effectively in older adults and is particularly important because life expectancy has increased in the U.S., increasing dramatically the number of older adults. Project 1uses a longitudinal design in older adults to examine the temporal stability of loneliness, the predictors of the experience of loneliness, and the physiological (e.g., autonomic) and behavioral (e.g., health behaviors, sleep) effects associated with loneliness. Project 2 uses national survey data and linked Medicare claims data to examine the origins and consequences of loneliness and stress in the social environment. Project 3 is an animal model of vulnerability to social isolation and disruption as an individual trait, identifying the specific hormonal and immunological sequelae that increase risk for infectious and malignant disease during aging. There are also two cores that provide broad support to the projects: Core A the administrative core, and Core B the data management and statistical management core.